Locke was a critic, philosopher, teacher, and arts patron. He edited The New Negro (1925), an anthology credited with starting the Harlem Renaissance.

Locke was the first African American Rhodes Scholar. He taught at Howard University from 1911 to 1916 and again from 1917 until his retirement in 1953, and was chair of the Philosophy Department. His books include Race Contacts and Interracial Relations (1916), The Negro in America (1933), and When Peoples Meet (co-edited with Bernhard J. Stern, 1942). Hewas one of the earliest American collectors of African Art, and his collection now forms the core of the Art Gallery at Howard.

Locke lived at 1309 R St. NW from 1912 through 1916. He moved away for a year to finish his PhD at Harvard, thenreturned in 1917 and rented a modest apartment in the same block at 1326 R St. NW. His mother, who had retired from teaching, joined him in thissecond address, and lived with Locke until her death in 1922. After that time, Locke stayed on at the same address on his own, until his own retirement from teaching in 1953. He died a year later, in New York City. In 2014, his ashes were interred in Congressional Cemetery.